Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations ...between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.
Highlights • Depression symptoms are often persistent among lung cancer patients. • Patient characteristics stratify risk for depression during cancer treatment. • Lung cancer patients with ...depression symptoms suffer significantly worse QOL. • Cancer symptoms and social support are important determinants for survival.
B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Each B cell expresses a single B cell receptor (BCR)
, and the diverse range of BCRs expressed by the ...total B cell population of an individual is termed the 'BCR repertoire'. Our understanding of the BCR repertoire in the context of immune-mediated diseases is incomplete, and defining this could provide new insights into pathogenesis and therapy. Here, we compared the BCR repertoire in systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Crohn's disease, Behçet's disease, eosinophilic granulomatosis with polyangiitis, and immunoglobulin A (IgA) vasculitis by analysing BCR clonality, use of immunoglobulin heavy-chain variable region (IGHV) genes and-in particular-isotype use. An increase in clonality in systemic lupus erythematosus and Crohn's disease that was dominated by the IgA isotype, together with skewed use of the IGHV genes in these and other diseases, suggested a microbial contribution to pathogenesis. Different immunosuppressive treatments had specific and distinct effects on the repertoire; B cells that persisted after treatment with rituximab were predominately isotype-switched and clonally expanded, whereas the inverse was true for B cells that persisted after treatment with mycophenolate mofetil. Our comparative analysis of the BCR repertoire in immune-mediated disease reveals a complex B cell architecture, providing a platform for understanding pathological mechanisms and designing treatment strategies.
Two-dimensional transition metal dichalcogenides (TMDs) provide a unique possibility to generate and read-out excitonic valley coherence using linearly polarized light, opening the way to valley ...information transfer between distant systems. However, these excitons have short lifetimes (ps) and efficiently lose their valley coherence via the electron-hole exchange interaction. Here, we show that control of these processes can be gained by embedding a monolayer of WSe
in an optical microcavity, forming part-light-part-matter exciton-polaritons. We demonstrate optical initialization of valley coherent polariton populations, exhibiting luminescence with a linear polarization degree up to 3 times higher than displayed by bare excitons. We utilize an external magnetic field alongside selective exciton-cavity-mode detuning to control the polariton valley pseudospin vector rotation, which reaches 45° at B = 8 T. This work provides unique insight into the decoherence mechanisms in TMDs and demonstrates the potential for engineering the valley pseudospin dynamics in monolayer semiconductors embedded in photonic structures.
Microplastics (MP), the debris that collectively refers to plastic fragments and particles of <5 mm in size within marine environments, has been the subject of interest within the past decade. ...Evidence of its occurrence and abundance, has been recorded in this communication after examining gastrointestinal specimens of eight commercially available fish species common to the Arabian (Persian) Gulf acquired locally from the State of Kuwait. The species studied belonged to different trophic levels, and the specimens were subjected to Micro Raman and Micro Fourier Infrared Spectroscopy (FTIR) in Attenuated Reflective Mode (ATR) to determine the presence and type of polymer of the MP. The detected MP set a president for the first time in the examined fish species within the State of Kuwait, which are of immense commercial importance. Various particles were detected, and three MP particles (fragments) were detected within the guts of Acanthopagrus latus, Eleutheronemaa tetradactylum and Lutjanus quinquelineatus. Based on the nature and behaviour of these particular fish types which prefer to stay in muddy waters and sheltered lagoons, it is suspected that common primary sources of MP (i.e. waste fragmentation) have led to passive/active intake (e.g. detritus ingestion) of these particles (fragments) by these species of fish in Kuwait.
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•Evidence of MP presence in fish guts is recorded in Kuwait•Eight different species were studied and acquired locally.•Evidence in three types of fish belonging to different trophic levels was recorded.•Polyethylene was determined to be the type of polymer constituting the MP.
Aims/hypothesis
In previous studies we have shown that extravasated, modified LDL is associated with pericyte loss, an early feature of diabetic retinopathy (DR). Here we sought to determine detailed ...mechanisms of this LDL-induced pericyte loss.
Methods
Human retinal capillary pericytes (HRCP) were exposed to ‘highly-oxidised glycated’ LDL (HOG-LDL) (a model of extravasated and modified LDL) and to 4-hydroxynonenal or 7-ketocholesterol (components of oxidised LDL), or to native LDL for 1 to 24 h with or without 1 h of pretreatment with inhibitors of the following: (1) the scavenger receptor (polyinosinic acid); (2) oxidative stress (
N
-acetyl cysteine); (3) endoplasmic reticulum (ER) stress (4-phenyl butyric acid); and (4) mitochondrial dysfunction (cyclosporin A). Oxidative stress, ER stress, mitochondrial dysfunction, apoptosis and autophagy were assessed using techniques including western blotting, immunofluorescence, RT-PCR, flow cytometry and TUNEL assay. To assess the relevance of the results in vivo, immunohistochemistry was used to detect the ER stress chaperon, 78 kDa glucose-regulated protein, and the ER sensor, activating transcription factor 6, in retinas from a mouse model of DR that mimics exposure of the retina to elevated glucose and elevated LDL levels, and in retinas from human participants with and without diabetes and DR.
Results
Compared with native LDL, HOG-LDL activated oxidative and ER stress in HRCP, resulting in mitochondrial dysfunction, apoptosis and autophagy. In a mouse model of diabetes and hyperlipidaemia (vs mouse models of either condition alone), retinal ER stress was enhanced. ER stress was also enhanced in diabetic human retina and correlated with the severity of DR.
Conclusions/interpretation
Cell culture, animal, and human data suggest that oxidative stress and ER stress are induced by modified LDL, and are implicated in pericyte loss in DR.
Determine global skin transcriptome patterns of early diffuse systemic sclerosis (SSc) and how they differ from later disease.
Skin biopsy RNA from 48 patients in the Prospective Registry for Early ...Systemic Sclerosis (PRESS) cohort (mean disease duration 1.3 years) and 33 matched healthy controls was examined by next-generation RNA sequencing. Data were analysed for cell type-specific signatures and compared with similarly obtained data from 55 previously biopsied patients in Genetics versus Environment in Scleroderma Outcomes Study cohort with longer disease duration (mean 7.4 years) and their matched controls. Correlations with histological features and clinical course were also evaluated.
SSc patients in PRESS had a high prevalence of M2 (96%) and M1 (94%) macrophage and CD8 T cell (65%), CD4 T cell (60%) and B cell (69%) signatures. Immunohistochemical staining of immune cell markers correlated with the gene expression-based immune cell signatures. The prevalence of immune cell signatures in early diffuse SSc patients was higher than in patients with longer disease duration. In the multivariable model, adaptive immune cell signatures were significantly associated with shorter disease duration, while fibroblast and macrophage cell type signatures were associated with higher modified Rodnan Skin Score (mRSS). Immune cell signatures also correlated with skin thickness progression rate prior to biopsy, but did not predict subsequent mRSS progression.
Skin in early diffuse SSc has prominent innate and adaptive immune cell signatures. As a prominently affected end organ, these signatures reflect the preceding rate of disease progression. These findings could have implications in understanding SSc pathogenesis and clinical trial design.
Pure red-cell aplasia and epoetin therapy Bennett, Charles L; Luminari, Stefano; Nissenson, Allen R ...
The New England journal of medicine,
09/2004, Letnik:
351, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Between 1988 and 1998, antibody-associated pure red-cell aplasia was reported in three patients who had undergone treatment with recombinant human erythropoietin (epoetin). Between 1998 and 2000, 13 ...such cases were reported from France--12 in patients who had received the Eprex formulation of epoetin alfa and 1 in a patient who had received Neorecormon (a formulation of epoetin beta); both are products that are marketed outside the United States.
We obtained reports of epoetin-associated pure red-cell aplasia from the Food and Drug Administration and from the manufacturers of Eprex, Epogen (another formulation of epoetin alfa), and Neorecormon. The numbers of case reports and estimates of exposure-adjusted incidence were analyzed according to the product, the cause of anemia, the route of administration, the country in which pure red-cell aplasia was identified, and the date on which pure red-cell aplasia was reported.
Between January 1998 and April 2004, 175 cases of epoetin-associated pure red-cell aplasia were reported for Eprex, 11 cases for Neorecormon, and 5 cases for Epogen. Over half these cases had occurred in France, Canada, the United Kingdom, and Spain. Between 2001 and 2003, the estimated exposure-adjusted incidence was 18 cases per 100,000 patient-years for the Eprex formulation without human serum albumin, 6 per 100,000 patient-years for the Eprex formulation with human serum albumin, 1 case per 100,000 patient-years for Neorecormon, and 0.2 case per 100,000 patient-years for Epogen. After procedures were adopted to ensure appropriate storage, handling, and administration of Eprex to patients with chronic kidney disease, the exposure-adjusted incidence decreased by 83 percent worldwide.
After the peak incidence of Eprex-associated pure red-cell aplasia was reached in 2001, interventions designed in response to drug-monitoring programs worldwide resulted in a reduction of more than 80 percent in the incidence of pure red-cell aplasia due to Eprex.
Abstract Background context Achieving solid implant fixation to osteoporotic bone presents a clinical challenge. New techniques and devices are being designed to increase screw–bone purchase of ...pedicle screws in the lumbar spine via a novel cortical bone trajectory that may improve holding screw strength and minimize loosening. Preliminary clinical evidence suggests that this new trajectory provides screw interference that is equivalent to the more traditionally directed trajectory for lumbar pedicle screws. However, a biomechanical study has not been performed to substantiate the early clinical results. Purpose Evaluate the mechanical competence of lumbar pedicle screws using a more medial-to-lateral path (ie, “cortical bone trajectory”) than the traditionally used path. Study design Human cadaveric biomechanical study. Methods Each vertebral level (L1–L5) was dual-energy X-ray absorptiometry (DXA) scanned and had two pedicle screws inserted. On one side, the traditional medially directed trajectory was drilled and tapped. On the contralateral side, the newly proposed cortical bone trajectory was drilled and tapped. After qCT scanning, screws were inserted into their respective trajectories and pullout and toggle testing ensued. In uniaxial pullout, the pedicle screw was withdrawn vertically from the constrained bone until failure occurred. The contralateral side was tested in the same manner. In screw toggle testing, the vertebral body was rigidly constrained and a longitudinal rod was attached to each screw head. The rod was grasped using a hydraulic grip and a quasi-static, upward displacement was implemented until construct failure. The contralateral pedicle screw was tested in the same manner. Yield pullout (N) and stiffness (N/mm) as well as failure moment (N-m) were compared and bone mineral content and bone density data were correlated with the yield pullout force. Results New cortical trajectory screws demonstrated a 30% increase in uniaxial yield pullout load relative to the traditional pedicle screws (p=0.080), although mixed loading demonstrated equivalency between the two trajectories. No significant difference in construct stiffness was noted between the two screw trajectories in either biomechanical test or were differences in failure moments (p=0.354). Pedicle screw fixation did not appear to depend on bone quality (DXA) yet positive correlations were demonstrated between trajectory and bone density scans (qCT) and pullout force for both pedicle screws. Conclusions The current study demonstrated that the new cortical trajectory and screw design have equivalent pullout and toggle characteristics compared with the traditional trajectory pedicle screw, thus confirming preliminary clinical evidence. The 30% increase in failure load of the cortical trajectory screw in uniaxial pullout and its juxtaposition to higher quality bone justify its use in patients with poor trabecular bone quality.
There is a need for better understanding of the risk of thrombocytopenic, haemorrhagic, thromboembolic disorders following first, second and booster vaccination doses and testing positive for ...SARS-CoV-2. Self-controlled cases series analysis of 2.1 million linked patient records in Wales between 7th December 2020 and 31st December 2021. Outcomes were the first diagnosis of thrombocytopenic, haemorrhagic and thromboembolic events in primary or secondary care datasets, exposure was defined as 0-28 days post-vaccination or a positive reverse transcription polymerase chain reaction test for SARS-CoV-2. 36,136 individuals experienced either a thrombocytopenic, haemorrhagic or thromboembolic event during the study period. Relative to baseline, our observations show greater risk of outcomes in the periods post-first dose of BNT162b2 for haemorrhagic (IRR 1.47, 95%CI: 1.04-2.08) and idiopathic thrombocytopenic purpura (IRR 2.80, 95%CI: 1.21-6.49) events; post-second dose of ChAdOx1 for arterial thrombosis (IRR 1.14, 95%CI: 1.01-1.29); post-booster greater risk of venous thromboembolic (VTE) (IRR-Moderna 3.62, 95%CI: 0.99-13.17) (IRR-BNT162b2 1.39, 95%CI: 1.04-1.87) and arterial thrombosis (IRR-Moderna 3.14, 95%CI: 1.14-8.64) (IRR-BNT162b2 1.34, 95%CI: 1.15-1.58). Similarly, post SARS-CoV-2 infection the risk was increased for haemorrhagic (IRR 1.49, 95%CI: 1.15-1.92), VTE (IRR 5.63, 95%CI: 4.91, 6.4), arterial thrombosis (IRR 2.46, 95%CI: 2.22-2.71). We found that there was a measurable risk of thrombocytopenic, haemorrhagic, thromboembolic events after COVID-19 vaccination and infection.
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